The Phenomenon of Persistence
I found an interesting article in Science Magazine the other day. It was published in September of 2004, but personally shed new insight into survival mechanisms that microbes use when challenged with antibiotics. We hear a lot about mutation of pathogens into different drug-resistant strains. And of course we know by DNA sequencing that the genetic machinery changes on an ongoing basis, and ultimately may drive errors that enhancement survivability.
But how do we explain the survival of a small percentage of a population of a genetically identical strain when exposed to a sufficiently lethal antibiotic dose? We know for example that the kill rate curve for E. coli starts as a fast exponential function, but then changes pattern to a slow, somewhat linear decline after a few hours. The resilient cells have not developed a genetic resistance, but are still able to survive extended exposure. After the drug is removed, the surviving cells regrow into a new colony that is equally sensitive to the antibiotic.
The answer can be attributed to a phenomenon called persistence. Researchers have demonstrated that within a population of genetically identical bacteria, some cells exist in “normal” fast-growth mode, while a small percentage (persistor cells) change phenotype into an arrested growth state. In this persistor mode, antibiotics are not effectively absorbed, and cells are less vulnerable.
From a practical standpoint, the big take-away from this lesson is that antimicrobial treatments need to consider the persistors as the limiting factor. Dosages aimed at the normal population will not be permanently effective, and will only stall the eventual re-establishment of the infection.